The cannabinoid receptor type-1 (CB₁), one of the most abundant G protein-coupled receptors in the central nervous system, is pivotal in regulating neuronal transmission and various fundamental physiological processes. Intriguingly, CB₁ can be functionally associated with mitochondrial membranes (mtCB₁) in multiple types of brain cells, thereby governing their energy fluxes. Via mtCB1, cannabinoids reduce mitochondrial activity and lactate production.      

Furthermore, CB₁ is expressed within glioblastoma (GBM), an aggressive and incurable form of brain malignancy characterized by robust metabolic adaptability. Extensive in vitro and in vivo investigations have demonstrated the substantial impact of cannabinoids on tumor growth and invasive properties; however, the exact mechanisms are not fully understood. Despite empirical observations highlighting the pro-apoptotic effect of CB₁ agonists, their role in mitochondrial functions and in cancer cell metabolism has remained an area of limited exploration.

Preliminary findings suggest the presence of mtCB₁ within patient-derived GBM cells, underscoring its potential as a compelling target for disrupting cancer cell metabolism and crucial actor in the anti-glioma effect of cannabinoids. Given its capacity to modulate both oxidative phosphorylation and glycolysis, mtCB₁ emerges as an intriguing candidate for therapeutic intervention within the context of GBM and its complex metabolic environment.

More information:

• https://www.researchgate.net/profile/Antonio-Pagano-Zottola